Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis and its complications. The fibrogenic process is consecutive to intense proliferation and accumulation of hepatic myofibroblasts that synthesize fibrosis components and inhibitors of matrix degradation [1]. Hepatic myofibroblasts play a key role in the development of liver fibrosis associated with chronic liver diseases, and their removal by apoptosis contributes to the resolution of liver fibrosis. Better understanding of the molecular mechanisms and signaling pathways that govern hepatic myofibroblast functions is a prerequisite for the identification of antifibrotic targets that will enable to develop liver-directed antifibrotic drugs. Along these lines, currently recognized antifibrotic strategies include: (i) reduction of hepatic myofibroblast accumulation by molecules that block their proliferation or stimulate their apoptosis, and/or (ii) reduction of fibrosis by agents that inhibit extracellular matrix synthesis or enhance its degradation.
Cannabinoids are the main constituent of marijuana and include psychoactive molecules, such as (−)Δ9-tetrahydrocannabinol (THC), and non psychoactive substances, like cannabidiol. Endogenous natural cannabinoids have also been characterized, anandamide and 2-arachidonyl glycerol ([(5Z,8Z,11Z,14Z)-5,8,11,14-Eicosatetraenoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl ester]), which are arachidonic acid-derived lipids [2, 23]. Cannabinoids display analgesic, antiemetic, vasorelaxing and anti-inflammatory properties, and stimulate food intake [3; 2]. They also exert antitumoral effects, mainly due to their antiproliferative and apoptotic properties [4]. Cannabinoid effects are mediated by activation of specific G protein-coupled receptors, CB1 and CB2 [5]. CB1 receptors are predominant in brain and are responsible for cannabinoid psychoactivity, whereas the peripheral CB2 receptors are mainly expressed in the immune system and are devoid of cannabinoid psychoactive effects [5]. Atypical CB receptors, distinct from CB1 and CB2 have been described in brain and in vascular endothelial cells.